Risk factors for sudden cardiac death to determine high risk patients in specific patient populations that may benefit from a wearable defibrillator

Table 1 Primary prevention implantable cardioverter defibrillator studies

Study	Intervention/control group	Inclusion criteria	Risk reduction of SCD with ICD
Multicenter Automatic Defibrillator Implantation Trial[12]	ICD vs antiarrhythmic drug	Previous MI; EF ≤ 35%; nsVT; positive findings on EPS	54% (P = 0.001)
Multicenter Unsustained Tachycardia Trial[13]	EP-guided therapy vs placebo	Coronary disease; EF ≤ 40%; Non-sustained VT; inducible VT at EPS	51% (P = 0.001)
Multicenter Automatic Defibrillator Implantation Trial 2[14]	ICD vs optimal pharmacological treatment	Prior MI EF ≤ 30%	31% (P = 0.02)
Sudden Cardiac Death in Heart Failure Trial[15]	ICD vs optimal pharmacological therapy vs optimal pharmacological therapy + amiodarone	Ischaemic and non-ischaemic cardiomyopathy; EF ≤ 35%	23% (P = 0.007)
Defibrillator implantation in patients with nonischemic systolic heart failure[16]	ICD vs optimal pharmacological therapy	Non-ischaemic cardiomyopathy; EF ≤ 35%	50% (P = 0.005)

SCD: Sudden cardiac death; ICD: Implantable cardioverter defibrillator; EF: Ejection fraction; EP: Electrophysiology; MI: Myocardial infarction; EPS: Electrophysiology studies; VT: Ventricular tachycardia.

Table 2 Secondary prevention implantable cardioverter defibrillator studies

Study	Intervention/control group	Inclusion criteria	Risk reduction with ICD
Antiarrhythmics Versus Implantable Defibrillators study[17]	ICD vs antiarrhythmic drugs	Resuscitated from near-fatal VF or post-cardioversion from sustained VT	28% (P = 0.02)
Canadian Implantable Defibrillator Study[18]	ICD vs amiodarone	Resuscitated VF or VT or with unmonitored syncope	20% (P = 0.14)
Cardiac Arrest Study Hamburg[19]	ICD vs amiodarone vs metoprolol	Survivors of cardiac arrest secondary to documented ventricular arrhythmias	23% (P = 0.08)

ICD: Implantable cardioverter defibrillator; VF: Ventricular fibrillation; VT: Ventricular tachycardia.

Table 3 Risk factors for sudden cardiac death post myocardial infarction

Risk factor studied	Relative risk of SCD	P value	Absolute SCD risk in cohort	Study size	Year	Country
Age
Rao et al[24]	OR 1.03 (1.00-1.05) (Increasing age)	0.0163	4.9% in the 1st month post MI	929	2012	India
Mehta et al[25]	OR 0.12; Standard error = 0.02 (Age per 1 year increase)	0.0001		2948	2001	North America
Abildstrom et al[26]	OR 1.56 (1.43–1.70) (Age per 10 years)	< 0.0001	5.3% at 1 year	5983	2002	Denmark
Female gender
Rao et al[24]	OR 1.78 (1.02-2.85)	0.0042	4.9% in the 1st month post MI	929	2012	India
Greenland et al[27]	OR 1.72 (1.45-2.04)	< 0.0005		5839	1991	Israel
Greenland et al[27]	OR 1.32 (1.05-1.66) (Death at 1 year)	< 0.03		5839	1991	Israel
Ghaffari et al[28]	OR 1.76 (1.22–2.54) (univariate analysis)	0.002		1017	2017	Iran
Ghaffari et al[28]	OR 1.19 (0.77–1.8) (multivariate analysis)	0.407		1017	2017	Iran
Macintyre et al[29]	OR 1.09 (1.06 to 1.13) (Death at 1 year)	< 0.00001		201114	2001	UK
Male gender
Abildstrom et al[26]	OR 1.34 (1.11–1.63)	< 0.005	5.3% at 1 year	5983	2002	Denmark
LV dysfunction
Rao et al[24]	OR 2.35 (1.09-5.03) (Severe LV dysfunction ≤ 30%)	0.0292	4.9% in the 1st month post MI	929	2012	India
Solomon et al[30]	HR 1.21 (1.10 to 1.30) (LV depression by each 5 percentage points)		7% at 1 month post MI; 11% at 2 years post MI	14609	2005	North America, Europe and New Zealand
Klem et al[31]	HR 6.30 (1.40-28.00) (LVEF > 30% and significant scarring > 5% on CMRI compared to no scarring)	0.02		137	2012	USA
Klem et al[31]	HR 3.90 (1.20-13.10) (LVEF ≤ 30% and those with scar > 5% on CMRI compared to those with scarring)	0.03		137	2012	USA
Yeung et al[32]	HR 3.60 (1.46–8.75) (LVEF ≤ 30%)	< 0.01		610	2012	China
Chitnis et al[33]	OR 4.51 (2.20–9.24) (LVEF ≤ 35%)	< 0.0001	4% in those with EF > 35% at 1 year post MI; 8% in those with EF≤ 35% at 1 year post MI	929	2014	India
Adabag et al[34]	HR 3.64 (1.71-7.75) (presence of heart failure based on the framingham criteria)	< 0.001		693	2008	USA
Right ventricular involvement
Mehta et al[25]	OR 3.20 (2.40-4.10)	< 0.00001		2948	2001	Canada
Diabetes
Yeung et al[32]	HR 1.90 (1.04–3.40)	0.04		610	2012	China
Junttila et al[35]	HR 3.80 (2.40–5.80)	< 0.001		3276	2010	Finland
Ventricular arrythmia
Maggioni et al[36]	RR 2.24 (1.22-4.08) (more than 10 premature ventricular beats per hour)	0.002		8676	1993	Italy
Maggioni et al[36]	RR 1.20 (0.80-1.79) (NSVT)			8676	1993	Italy
Mäkikallio et al[37]	HR 2.40 (1.30–4.40) (Ventricular premature complexes 10/h)	0.0049		2130	2005	Finland
Mäkikallio et al[37]	HR 3.30 (1.70–6.50) (NSVT)	< 0.0005		2130	2005	Finland
ECG features
Mäkikallio et al[37]	HR 3.30 (1.70–6.50) (QRS ≥ 120 ms)	0.0004		2130	2005	Finland
Zimetbaum et al[38]	HR 1.44 (1.11-1.88) (Non-specific intraventricular conduction delay)	0.0069		1638	2004	USA
Zimetbaum et al[38]	HR 1.49 (1.02-2.17) (LBBB)	0.0400		1638	2004	USA
Zimetbaum et al[38]	HR 1.35 (1.08-1.69) (LVH)	0.0082		1638	2004	USA
Siscovick et al[39]	OR 1.40 (1.00-2.00) (LVH)	0.02		688	1996	USA

SCD: Sudden cardiac death; MI: Myocardial infarction; HR: Hazard ratio; OR: Odds ratio; LV: Left ventricular; EF: Ejection fraction.

Table 4 Risk factors for sudden cardiac death in heart failure

Risk factor studies	Relative risk of SCD	P value	Absolute SCD risk in cohort	Study size	Year	Country
Age
Lee et al[40]	OR 1.70 (1.45-1.99) (Age per 10 unit increase)	< 0.001		4031	2003	Canada
Cowie et al[41]	HR 1.26 (1.01 to 1.57) (Age per 10 year increase)	0.04		220	2000	UK
Taylor et al[42]	HR 1.10 CI 1.09–1.10 (Increasing age)			6162	2012	UK
Male gender
Taylor et al[42]	HR 1.50 (1.36–1.66)			6162	2012	UK
Vaartjes et al[43]	HR 1.21 (1.14-1.28) at 28 d; HR 1.26 (1.21-1.31) at 1 year; HR 1.28 (1.24-1.31) at year 5			29053	2010	Netherlands
Comorbidities
Lee et al[40]	OR 1.43 (1.03-1.98) 30-day mortality (Cerebrovascular disease)	0.03		4031	2003	Canada
Lee et al[40]	OR 1.66 (1.22-2.27) (COPD)	0.002		4031	2003	Canada
Lee et al[40]	OR, 3.22 (1.08-9.65) (Cirrhosis)	0.04		4031	2003	Canada
Lee et al[40]	OR 2.54 (1.77-3.65) (Dementia)	< 0.001		4031	2003	Canada
Lee et al[40]	OR 1.86 (1.28-2.70) (Cancer)	0.001		4031	2003	Canada
Yoshihisa et al[44]	HR 3.01 (1.11–8.63) (COPD)	0.038		378	2014	Japan
Fisher et al[45]	RR 1.10 (1.06-1.14) Death at 1 year; RR 1.40 (1.28-1.52) death at 5 years (COPD)			9748	2015	USA
Atrial fibrillation
Taylor et al[44]	HR 1.55 (1.26–1.92)			6162	2012	UK
Ahmed et al[46]	HR 1.41 (1.08-1.83)			944	2005	USA
Corell et al[47]	HR 1.38 (1.07-1.78)	0.01		1019	2007	Denmark
Middlekauff et al[48]	HR 0.89 (0.55-1.23)	0.013		390	1991	USA
Ventricular arrythmia
Doval et al[49]	RR 2.77 (1.78-4.44) (NSVT)	< 0.001	23.7% at 2 years in those with NSVT; 8.8% at 2 years in those without NSVT	516	1996	Argentina
Doval et al[49]	RR 3.37 (1.57-7.25) (Couplets)	< 0.0005	23.7% at 2 years in those with NSVT; 8.8% at 2 years in those without NSVT	516	1996	Argentina
Teerlink et al[50]	RR 1.16 (1.09–1.24) (NSVT)	0.001	13% at 2 years	1080	2000	USA
Szabó et al[51]	RR 3.50 (1.54-7.98) (VT)	0.003		211	1994	Netherlands
Szabó et al[51]	RR 2.68 (1.11-6.48) (Freq. VT > 144 beats/min)	0.029		211	1994	Netherlands
Szabó et al[51]	RR 3.89 (1.61-9.43) (Length VT > 2s)	0.003		211	1994	Netherlands
Echocardiographic variables
Taylor et al[42]	HR 1.80 (1.55–2.10) (EF < 40% vs > 50%)			6162	2012	UK
Taylor et al[42]	HR 1.29 (1.11–1.50) (EF 40%–50% vs > 50%)			6162	2012	UK
Shadman et al[52]	OR 1.15 (EF per 10% decrease)	0.005		9885	2015	USA
Quiñones et al[53]	RR 2.75 (1.62-4.66) (1-SD difference in LV Mass)	0.0002		1209	2000	USA
Quiñones et al[53]	RR 1.84 (1.08-3.15) (1-SD difference in LA Diameter)	0.03		1209	2000	USA
Quiñones et al[53]	RR 2.73 (1.43-5.20) (1-SD difference in lv end systolic dimension)	0.003		1209	2000	USA
Grayburn et al[54]	HR 1.01 (1.00–1.01) (LV end-diastolic volume index)	0.0012		336	2005	USA
Deranged kidney function
Grayburn et al[54]	HR 2.023 (1.24–3.32)	0.0052		336	2005	USA
Cowie et al[41]	HR 2.64 (1.87-3.74)	< 0.001		220	2000	UK

SCD: Sudden cardiac death; HR: Hazard ratio; OR: Odds ratio; LV: Left ventricular; EF: Ejection fraction.

Table 5 Risk factors for sudden cardiac death in the long QT syndrome

Risk factor studied	Relative risk of SCD	P value	Absolute SCD risk in cohort	Study size	Year	Country
Female gender
Sauer et al[55]	HR 2.68 (1.10–6.50)	< 0.05	Risk between ages of 18-40: LQTS1 4.9%; LQTS2 8.0%; LQTS3 4.9%	812	2007	USA
QTc interval
Sauer et al[55]	HR 3.34 (1.49–7.49) (QTc 500–549 ms vs ≤ 499 ms)	< 0.01	Risk between ages of 18-40: LQTS1 4.9%; LQTS2 8.0%; LQTS3 4.9%	812	2007	USA
Sauer et al[55]	HR 6.35 (2.82–14.32) (QTc ≥ 550 ms vs ≤ 499 ms)	< 0.01	Risk between ages of 18-40: LQTS1 4.9%; LQTS2 8.0%; LQTS3 4.9%	812	2007	USA
Moss et al[56]	HR 1.05 (1.02-1.09) (QTc per 0.01 units)	< 0.01		1496	1991	USA
Priori et al[57]	RR 5.34 (2.82-10.13) [QTc in the third quartile (469 to 498 ms)]		Risk between ages 12-40 was 13% over 28 years	580	2003	Italy
Priori et al[57]	RR 8.36 (2.53-27.21) [QTc in the highest quartile (more than 498 ms)]		Risk between ages 12-40 was 13% over 28 years	580	2003	Italy
Goldenberg et al[58]	HR 36.53 (13.35–99.95) (LQTS with prolonged QTc interval vs unaffected family members)	< 0.001		3386	2012	USA, Europe, Japan and Israel
Goldenberg et al[58]	HR 10.25 (3.34–31.46) (LQTS with normal-range QTc interval vs unaffected family members)	< 0.001		3386	2012	USA, Europe, Japan and Israel
Previous history of cardiac events
Sauer et al[55]	HR 5.10 (2.50–10.39) (Interim time dependant syncope vs no interim syncope)	< 0.01	Risk between ages of 18-40: LQTS1 4.9%; LQTS2 8.0%; LQTS3 4.9%	812	2007	USA
Moss et al[56]	HR 3.10 (1.30-7.20) (History of cardiac event)	< 0.01		1496	1991	USA
Genotype
LQTS 3
Priori et al[57]	RR 2.76 (1.01-7.51) (Male sex)		Risk between ages 12-40 was 13% over 28 years	580	2003	Italy
Priori et al[57]	RR of 1.80 (1.07-3.04) (mutation at the LQT3 locus)		Risk between ages 12-40 was 13% over 28 years	580	2003	Italy
LQTS 2
Priori et al[57]	RR 1.61 (1.16-2.25) (LQT2 locus)		Risk between ages 12-40 was 13% over 28 years	580	2003	Italy
LQTS 1
Goldenberg et al[58]	HR 9.88 (1.26–37.63) (LQTS 1 mutation and normal QTc)	0.03		3386	2012	USA, Europe, Japan and Israel
Heart rate
Moss et al[56]	HR 1.02 (1.00-1.03) (Resting heart rate less than 60 beats/min)	0.01		1496	1991	USA
Niemeijer et al[59]	Bazett: HR 2.23 (1.17-4.24) Fridericia: HR 6.67 (2.96-15.06) (Consistent Qtc interval prolongation)			3484	2015	Netherlands

SCD: Sudden cardiac death; LQTS: Long QT syndrome; QTc: QT corrected interval; HR: Hazard ratio; OR: Odds ratio; LV: Left ventricular; EF: Ejection fraction.

Table 6 Risk factors for sudden cardiac death in patients with hypertrophic cardiomyopathy

Risk factor studied	Relative risk of SCD	P value	Absolute SCD risk in cohort	Study size	Year	Country
Age
O’Mahony et al[60]	HR 0.99 (0.98-1.00) (Age 42 ± 15)	0.007	5% at 5 years	3675	2014	Europe
Syncope
Liu et al[61]	HR 2.31 (1.22-4.38)			12146	2017	USA, China
O’Mahony et al[60]	HR 2.33 (1.69-3.19)	< 0.001	5% at 5 years	3675	2014	Europe
Christiaans et al[62]	HR 2.68 (0.97–4.38)			9357	2010	Netherlands, UK
Family history of SCD
Christiaans et al[62]	HR 1.27 (1.16–1.38)			9357	2010	Netherlands, UK
O’Mahony et al[60]	HR 1.76 (1.32-2.24)	<0.001	5% at 5 years	3675	2014	Europe
Liu et al[61]	HR 2.34 (1.46- 3.75)			12146	2017	USA, China
Abnormal blood pressure response during exercise
Liu et al[61]	HR 1.38 (0.65-2.89) (BP dropping on excersice)			12146	2017	USA, China
Christiaans et al[62]	HR 1.30 (0.64–1.96) (BP dropping on excersice)			9357	2010	Netherlands, UK
Non sustained ventricular tachycardia
Liu et al[61]	HR 2.92 (1.97-4.33)			12146	2017	USA, China
Sugrue et al[63]	HR 3.36 (1.00-11.35)	0.05		52	2017	USA
O’Mahony et al[60]	HR 2.53 (1.85-3.47)	< 0.001	5% at 5 years	3675	2014	Europe
Christiaans et al[62]	HR 2.89 (2.21–3.58)			9357	2010	Netherlands, UK
Left ventricular wall thickness/hypertrophy
Liu et al[61]	HR 3.17 (1.64-6.12) (Maximum LV wall thickness ≥  30 mm)			12146	2017	USA, China
Maeda et al[64]	HR 1.21 (1.04–1.39) (Maximum left ventricular wall thickness per 1-mm increase)	0.011		593	2016	Japan
O’Mahony et al[60]	HR 1.05 (1.03-1.07) (Maximal LV wall thickness in mm 21.5 ± 6)	< 0.001	5% at 5 years	3675	2014	Europe
Christiaans et al[62]	HR 3.10 (1.81–4.40) (LVH ≥ 20 mm)			9357	2010	Netherlands, UK
Left ventricular outflow tract obstruction
Liu et al[61]	HR 2.41 (1.55-3.73)			12146	2017	USA, China
O’Mahony et al[60]	HR 1.01 (1.00-1.01) [LVOT Gradient mmHG 18 (6-58)]	0.005	5% at 5 years	3675	2014	Europe
Left atrial diameter
O’Mahony et al[60]	HR 1.04 (1.02-1.05) (LA diameter in mm 46.2 ± 9)	< 0.001	5% at 5 years	3675	2014	Europe

SCD: Sudden cardiac death; LVOT: Left ventricular outflow tract; HR: Hazard ratio; OR: Odds ratio; LV: Left ventricular; EF: Ejection fraction.

Table 7 Summary of wearable cardioverter defibrillator studies

Study	General findings	Survival post shock
Wearable cardioverter-defibrillator use in patients perceived to be at high risk early post-myocardial infarction[65]	99 out of 8453 patients received 114 inappropriate shocks. None of the inappropriate shocks induced arrhythmias. The inappropriate shock rate was 0.006 shocks per patient month of use.	67% for those with VT/VF; 62% for those treated for PMVT/VF
Aggregate national experience with the wearable cardioverter defibrillator vest: event rates, compliance and survival[66]	Inappropriate shocks occurred in 67/3569 (1.9%) patients	90% for VT/VF events; 73.6% for all events
Vest Prevention of Early Sudden Death Trial[67]	Inappropriate shocks: 0.6%; Appropriate shocks: 1.4%; Hours/day WCD worn: 14.1	Risk of SCD (WCD vs Control): 1.6% vs 2.4%, P = 0.18. All-cause mortality (WCD vs Control): 3.1% vs 4.9%, P = 0.04

VT: Ventricular tachycardia; VF: Ventricular fibrillation; WCD: Wearable cardioverter defibrillator; SCD: Sudden cardiac death.